Fludrocortisone 850micrograms/5ml oral suspension

[This corrects the article DOI: 10.3389/fmed.2026.1755626.].

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PurposeTo evaluate the efficacy and safety of hydrocortisone combined with fludrocortisone in the treatment of septic shock in adults.MethodsWe searched PubMed, Embase, Web of Science, and the Cochrane Library for studies on hydrocortisone combined with fludrocortisone in the treatment of septic shock in adults. Two investigators independently screened studies, extracted data, and assessed the risk of bias of the included studies. A meta-analysis was performed using RevMan 5.3 and STATA 17.0 software.ResultsA total of eight studies (5 RCTs and 3 N-RCTs) were included. Stratified analysis by study design and comparator type revealed that in the HC + FC vs. Placebo subgroup (derived solely from RCTs), the combination significantly reduced 28-day mortality [RR 0.84; 95% CI (0.76, 0.94); p = 0.002], 90-day mortality [RR 0.82; 95% CI (0.71, 0.94); p = 0.006], and in-hospital mortality [RR 0.85; 95% CI (0.77, 0.94); p = 0.002]. In contrast, for the HC + FC vs. HC alone subgroup (addressing incremental benefit), no significant survival advantage was observed in either RCTs (n = 553) or N-RCTs (n = 88,666, 28-day mortality RR 0.99, p = 0.79). Regarding safety, HC + FC was associated with a higher reinfection rate compared to placebo (RR 1.13, p = 0.03) but not when compared to HC alone (p = 0.19). No significant increase in gastrointestinal bleeding or reduction in ICU/hospital length of stay was identified across all tiers of evidence.ConclusionEvidence primarily from RCTs indicates that HC + FC is associated with improved survival compared to placebo in septic shock. However, large-scale observational data suggest no significant incremental benefit over hydrocortisone alone. While the combination appears safe regarding gastrointestinal bleeding, the increased reinfection risk compared to placebo warrants caution. Given the non-causal nature of observational findings, these results are suggestive rather than definitive. Future head-to-head trials are essential to confirm the marginal efficacy of fludrocortisone supplementation.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251001999, Identifier: CRD420251001999.

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BackgroundThe therapeutic benefit of corticosteroids in managing sepsis and septic shock remains controversial, particularly concerning optimal dosing strategies and the role of adjunctive fludrocortisone. Recent large-scale trials and updated guidelines underscore the need for a dose-stratified synthesis. This meta-analysis aimed to comprehensively evaluate the effects of corticosteroids on short-term mortality in sepsis, with subgroup analyses by steroid type, dosage, and geographic region.MethodsThis study followed the PRISMA 2020 guidelines. Randomized controlled trials (RCTs) comparing corticosteroids with placebo in adult patients with sepsis or septic shock were included. Subgroup analyses were pre-specified for daily hydrocortisone-equivalent dose (≤ 200 mg, 201-300 mg, > 300 mg), steroid type (hydrocortisone alone vs. hydrocortisone plus fludrocortisone), and region (China vs. non-China). Risk ratios (RRs) with 95% confidence intervals (CIs) were synthesized using a random-effects model.ResultsEighteen RCTs comprising 7,982 patients were included. Corticosteroid therapy was associated with reduced 28-day mortality (RR = 0.88; 95% CI: 0.79-0.98; I² = 39%). The 28-day mortality was 31.0% in the corticosteroid group versus 35.5% in the control group.The most pronounced benefit was seen with 201-300 mg/day regimens (RR = 0.86; I² = 0%) and with combination therapy including fludrocortisone (RR = 0.89). Regional analysis showed weaker effects in trials conducted in China.ConclusionModerate-dose corticosteroids, especially when used in conjunction with fludrocortisone, significantly reduce short-term mortality in septic shock. Findings support guideline-endorsed steroid use and highlight the importance of individualized treatment strategies.

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